Sickle cell anemia is usually diagnosed at birth through routine newborn screening. In the United States, every state tests newborns for sickle cell disease as part of a standard blood test performed within the first few days of life. For babies born in countries without universal screening, or for adults who were never tested, diagnosis involves the same type of blood work and sometimes genetic testing to confirm the specific type of sickle cell disease.
Newborn Screening
A small blood sample, typically taken from the baby’s heel, is collected shortly after birth. The lab analyzes this sample to identify the different types of hemoglobin present, the protein in red blood cells that carries oxygen. In sickle cell disease, the body produces an abnormal form called hemoglobin S instead of the normal hemoglobin A.
Labs use one of three main techniques to separate and identify hemoglobin types. Isoelectric focusing (IEF) places the blood sample on a gel with a pH gradient, where each hemoglobin type migrates to a specific position based on its electrical charge, producing sharp, distinct bands that are easy to read. High-performance liquid chromatography (HPLC) separates hemoglobin types by passing the sample through a column and measuring how quickly each variant emerges. Capillary electrophoresis works on a similar principle, using an electric field to sort hemoglobin variants by size and charge. All three methods can detect hemoglobin S, hemoglobin C, and other clinically important variants, and they can also pick up carriers who have one copy of the gene but don’t have the disease.
Results from newborn screening are sent to your baby’s primary care provider. A positive screen typically leads to a referral to a pediatric hematologist for confirmatory testing and ongoing care.
Confirmatory Testing After a Positive Screen
A positive newborn screen is not the final diagnosis. Because screening methods occasionally produce unclear results, especially in premature infants or those who’ve received blood transfusions, a second round of testing confirms the finding. This usually involves repeating the hemoglobin analysis on a new blood sample, sometimes using a different lab technique than the initial screen.
In some cases, genetic testing is used to look directly at the hemoglobin beta (HBB) gene for the sickle cell mutation. This is particularly useful when the protein-based hemoglobin tests are ambiguous, or when doctors need to distinguish between different forms of sickle cell disease. Full sequencing of the HBB gene can also detect other variants like hemoglobin C or beta thalassemia mutations, which affect how severe the disease will be. One important note: an older test called the sickle prep or solubility test is not sufficient on its own to confirm or rule out sickle cell disease or sickle cell trait.
Sickle Cell Disease vs. Sickle Cell Trait
One of the most important distinctions the diagnostic process makes is between sickle cell disease and sickle cell trait. A person with sickle cell trait carries one copy of the hemoglobin S gene and one normal copy. Their blood typically contains less than 35% hemoglobin S, with the rest being normal hemoglobin A. They usually have no symptoms and live normal lives, though very high levels of hemoglobin S (around 34% or above) slightly increase the risk of certain kidney complications.
A person with sickle cell disease (the most common form being HbSS) inherits two copies of the hemoglobin S gene, one from each parent. Their red blood cells contain mostly hemoglobin S with little to no hemoglobin A. The hemoglobin analysis clearly shows this difference in proportions, making it straightforward for the lab to distinguish between the two.
When Symptoms Lead to Diagnosis
In countries without universal newborn screening, sickle cell disease is often first suspected when symptoms appear. In infants and toddlers, painful swelling in the hands and feet, called dactylitis or hand-foot syndrome, is usually the earliest sign. Sickle-shaped red blood cells get stuck in the tiny blood vessels of the hands and feet, blocking blood flow and causing swelling, pain, and often fever. This typically shows up between 6 months and 2 years of age, as the protective fetal hemoglobin that all babies are born with gradually decreases.
Other early warning signs include unexplained anemia, jaundice (yellowing of the skin and eyes), or an enlarged spleen. Any of these findings in a young child, especially one of African, Mediterranean, Middle Eastern, or South Asian descent, should prompt hemoglobin testing.
Diagnosis in Adults
Most people with sickle cell disease in the U.S. are diagnosed at birth. But adults who were born in countries without screening programs, or who immigrated after the newborn period, may reach adulthood without a diagnosis. The same blood tests used for newborns work in adults: hemoglobin analysis identifies the types and proportions of hemoglobin present, and genetic testing can confirm the specific mutation if needed.
Adults who’ve experienced recurrent pain crises, chronic anemia, or unexplained organ damage may be tested for the first time during a medical evaluation for these symptoms. The process is the same: a standard blood draw, hemoglobin analysis, and if necessary, genetic confirmation.
Prenatal and Preconception Testing
Parents who know they carry the sickle cell trait can find out whether their baby has sickle cell disease before birth. Chorionic villus sampling, performed between 8 and 12 weeks of pregnancy, takes a tiny tissue sample from the placenta to analyze the baby’s DNA. Amniocentesis, done around 16 weeks, examines DNA from cells floating in the amniotic fluid. Both procedures can definitively identify the sickle cell mutation. Researchers are also working on methods to detect fetal DNA circulating in the mother’s blood, which would avoid the small procedural risks of sampling the placenta or amniotic fluid.
Before pregnancy, carrier screening through a simple blood test can tell both partners whether they carry the hemoglobin S gene. If both parents are carriers, each pregnancy has a 25% chance of producing a child with sickle cell disease. This information helps families plan and prepare.
Rapid Testing in Low-Resource Settings
In parts of sub-Saharan Africa and South Asia where sickle cell disease is most common, access to the lab equipment needed for standard hemoglobin analysis can be limited. Rapid point-of-care tests are filling this gap. One such test, SICKLECHECK, was evaluated at a hospital in Kenya and showed strong accuracy: 98.95% sensitivity for detecting sickle cell disease and 90.48% sensitivity for identifying carriers. These lateral-flow tests work similarly to a pregnancy test, producing results from a finger-prick blood sample in minutes without electricity or specialized training. For millions of people born far from a reference laboratory, rapid tests like these offer the first realistic path to early diagnosis.